Research projects initiated during the past three years will be continued in areas relating to mechanism of thyroid hormone biosynthesis, mechanism of hormone secretion, and mechanism of thyroid hormone uptake by cells and metabolic action in cells. Peroxidase will be purified using a novel affinity chromatography technique; peroxidase enzyme will be localized using immunospecific antibodies. Sources of H2O2 in the thyroid will be studied by using antibodies directed against specific intracellular enzymes related to H2O2 generation. Patients with abnormalities of thyroid hormone synthesis or action will be studied in detail. Mechanisms governing thyroid hormone biosynthesis, including iodide transport, peroxidase activity, H2O2 generation, and thyroglobulin synthesis will be investigated in animals. Mechanism of T3 action will be investigated by studies on the ability of the nuclear T3 binding protein to alter functional activity of liver nuclear polymerase in vitro. Patients with defective nuclear hormone binding sites and hormone resistance will be studied clinically. Action of T3 on liver nuclear protein synthesis and protein phosphorylation will be studied. The possible role of phosphokinase in mediating the action of T3 on nuclear polymerase will be investigated. Lymphocyte T3 receptors will be studied in patients who have reduced serum T3 in response in stress, starvation, or steroids.